Geriatric depression is a significant public health problem as it is associated with disability in the performance of activities of daily living, with a dramatic increase in the rate of completed suicide and with greater mortality in the medically ill elderly. The clinical response to antidepressant treatment in geriatric depressed patients is delayed and the course of antidepressant response is highly variable. Even though there are effective antidepressant agents available, some patients are still refractory to treatment. An understanding of the neurobiology of geriatric depression, particularly of the serotonin function, may have implications for the clinical management of this disorder. The ability to study serotonergic function in vivo has been limited by the lack of safe and selective pharmacologic agents and limitations of the available serotonin radiotracers. The principal investigator and her colleagues have developed a direct and non-invasive method of measuring serotonergic function in vivo. These considerations provided the impetus for the proposed study to evaluate the pathophysiology of the serotonin system in normal aging and in geriatric depression using Positron Emission Tomography (PET) methods to measure the cerebral metabolic response to the acute, intravenous administration of a selective serotonin reuptake inhibitor (citalopram, celexa), as well as to chronic treatment with the oral medication. PET studies of cerebral glucose metabolism are sensitive to detecting functional anatomic changes and are sensitive to the effects of antidepressant treatment in depressed patients. The significance of the proposed studies is underscored by the lack of functional neuroanatomic data and the lack of in vivo neurobiologic studies of serotonin function in geriatric depression. The proposed studies will provide fundamental data regarding the functional neuroanatomy of geriatric depression and the functional responsiveness of the serotonin system, based on the evaluation of acute and chronic serotonin reuptake inhibition. As glucose metabolic activity represents the final common pathway of neurochemical activity in the brain, these findings would direct subsequent studies to characterize the neurochemical pathways underlying the regional changes using PET and neuroreceptor radiotracers.